Subtle speech changes may be first symptoms of Huntington’s: Study
Deficits linked to age of patient and number of CAG repeats
Subtle changes in speech are present before obvious symptoms of Huntington’s disease appear, and could potentially be a quantitative biomarker for the neurodegenerative disorder, a small study found.
The changes in speaking identified among Huntington’s patients were linked to age and an individual’s number of disease-causing CAG repeats — as well as to problems with cognitive and motor function.
“Speech deficits are detectable already in [early] stages of [Huntington’s] and are associated with other motor and cognitive deficits,” the researchers wrote, also noting that such changes are fairly easy to measure.
“Automated acoustic analysis provides an inexpensive, non-invasive way to assess [Huntington’s disease] repeatedly, without sophisticated technical equipment, that is scalable across languages,” the team wrote.
The study, “Speech biomarkers in Huntington disease: a cross-sectional study in pre-symptomatic, prodromal and early manifest stages,” was published in the European Journal of Neurology.
Speech deficits found to be among earliest symptoms of Huntington’s
Huntington’s is caused by an excess of repeats, called CAG triplets, within the HTT gene that provides instructions to produce a protein called huntingtin. Having 36 or more CAG triplets leads to the production of an abnormally long huntingtin protein that forms toxic clumps and causes nerve damage.
Many people with Huntington’s experience a lack of motor control. There may be chorea — involuntary and abrupt movements long associated with the disease — slowness of movement (bradykinesia), and stiffness.
Motor problems also can make it hard to speak. Some people develop slurred or slow speech, known as dysarthria, in the disease’s prodromal phase, which is characterized by the presence of early signs and nonspecific symptoms of Huntington’s. However, such subtle changes in speech may be difficult to detect.
To find out when subtle speech changes first appear, a team of researchers in the Czech Republic and Germany recorded speech samples from 69 people, ages 22-76, who carried at least 36 CAG repeats in one of the HTT gene’s copies.
Among them, 25 had manifest Huntington’s, which means they showed the disease’s hallmark motor symptoms. Another 15 were in the prodromal stage, and 29 were presymptomatic, meaning they as yet had no symptoms of Huntington’s.
The researchers ran the speech recordings through an automated acoustic analysis of 10 speech dimensions, and compared the data with those from 25 healthy people, ages 27-78, who served as controls.
The results showed that those with prodromal or manifest Huntington’s scored significantly higher than the controls in the composite dysarthria index (CDI), a combination of all 10 speech dimensions in which higher scores represent more severe speech changes.
The same was observed for perceptual dysarthria score (PDS), a subjective measure of speech changes where higher scores reflect severe dysarthria. Also, “perceptual and acoustic speech severity analyses were strongly correlated,” the team wrote.
However, there were no significant differences in CDI or PDS scores between people with presymptomatic Huntington’s and healthy controls.
Across the manifest and prodromal Huntington’s groups, there were changes in six of the 10 speech dimensions. Two of them — irregularities in performing rapid alternating motor speech movements and prolonged pauses — were only observed in the manifest group.
Slower speech rate, slower alternating motor speech movements, increased loudness variability, and unstable steady-state position of articulators — reflecting the positioning of the tongue, lips, and teeth — were observed in both the prodromal and manifest groups.
By using combinations of these speech dimensions, the researchers could tell people with manifest Huntington’s from healthy controls with a sensitivity of 92% and a specificity of 88%. A test’s sensitivity is its ability to correctly identify those with a given disease, while specificity refers to correctly identifying those without it.
It also was possible for researchers to tell people with prodromal Huntington’s from healthy controls with a sensitivity of 85% and a specificity of 79%.
1st study to track speech symptoms of Huntington’s
Higher scores in the CDI or PDS were each significantly associated with worse bradykinesia and slower thinking in premanifest stages — a merging of the presymptomatic and prodromal groups — and in manifest Huntington’s patients. Similar links were found with worse chorea in the manifest group alone.
As such, “speech abnormalities in [Huntington’s] are associated with other motor and cognitive deficits and are measurable already in premanifest stages,” the researchers wrote.
This study provides the first attempt to characterize speech alterations from [presymptomatic Huntington’s] to [prodromal Huntington’s] to early-stage [manifest Huntington’s], comparing subjective perceptual analysis by experts head-to-head with objective acoustic analysis.
Moreover, a higher CDI score was linked to a higher CAP score, which works as a measure of exposure to the expansion mutation. The CAP score derives from a formula that accounts for CAG repeat number and a person’s age; it results in higher scores with older age and longer CAG repeats.
“This study provides the first attempt to characterize speech alterations from [presymptomatic Huntington’s] to [prodromal Huntington’s] to early-stage [manifest Huntington’s], comparing subjective perceptual analysis by experts head-to-head with objective acoustic analysis,” the team wrote.
“Both types of analysis were mutually supportive in demonstrating dysarthria already in the prodromal stage of [Huntington’s disease],” they added.
According to the team, early speech changes “might represent a quantitative [Huntington’s] biomarker with potential for assessing disease progression.”
“Future work should focus on extending our findings in a longitudinal design while correlating speech changes with brain structures by magnetic resonance imaging,” the researchers concluded.